RE-irradiation of Diffuse MIdline Glioma paTients

Not Applicable

Not yet recruiting

• Conditions: Diffuse Intrinsic Pontine Glioma; Diffuse Glioma; Brain Tumor, Pediatric; Diffuse Midline Glioma, H3 K27M-Mutant; Thalamic Tumor; Pontine Tumors
• Interventions: Radiation: Re-irradiation

• Registration Number: NCT06093165
• Lead Sponsor: Rigshospitalet, Denmark

Brief Summary

The REMIT (RE-irradiation of diffuse MIdline glioma paTients) study evaluates safety and the palliative efficacy of re-irradiation of patients with diffuse midline glioma (DMG). The study will introduce a standard re-irradiation treatment schedule for DMG patients who have progressed following primary treatment.

Detailed Description

REMIT is a non-randomized, prospective, investigator-initiated, phase II, multi-centre observational study with two inclusion groups, arm A and B. Arm A and B will be offered the same treatment.

Patients treated with primary radiotherapy 54Gy/30 fractions, either enrolled in the BIOMEDE 2.0 protocol or not, will be included in Arm A. DMG patients treated with any other total dose and fractionation than 54Gy/30F will be included in Arm B. The re-RT and follow up will be the same in both arms.

As treatment 20Gy/10 fractions is given as first time re-irradiation with extended follow up on toxicity, performance status and quality of life.

Study Timeline

• Study First Submitted: 2023-09-08
• Status Verified: 2023-10
• Study Start: 2023-10
• Study First Submitted QC: 2023-10-16
• Last Update Submitted: 2023-10-16
• Study First Posted: 2023-10-23
• Last Update Posted: 2023-10-23
• Primary Completion: 2029-11
• Study Completion: 2029-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

• Diffuse midline glioma diagnosis: verified radiologically or histologically Biopsy is not mandatory for REMIT
• Age ≥ 12 months to ≤21 years.
• Min. 180 days/6 months have elapsed from the first day of the 1st RT course
• 1st course of radiotherapy
• Full recovery from all acute and subacute toxicities of 1st RT course
• Clinical progression of symptoms and/or radiographic progression
• Karnofsky performance status scale or Lansky Play Scale > 50% The performance status should not take the neurological deficits per se into account.

NB: Children and adults with a worsening performance status due to glioma-related motor deficit can be included.

• Life expectancy > 12 weeks after start of reRT
• Signed informed consent by patient and/or parents or legal guardian

Exclusion Criteria

• Presence of leptomeningeal spread or multifocal disease on MRI at progression
• Other co-morbidity that according to the treating physician would impair participation in the study
• >1 course of radiotherapy
• Neurofibromatosis type 1
• Inability to complete the medical follow-up (geographic, social, or mental reasons)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Re-irradiation	Primary radiotherapy 54Gy/30 fractions
B	Re-irradiation	Any other dose and fractionation for primary radiotherapy than 54gy/30 fractions.

Primary Outcome Measures

Name	Time	Method
To evaluate the safety of re-irradiation (reRT)	4 weeks after end of re-irradiation	The primary endpoint will be the cumulative incidence of grade ≥4 CTCAE (The NCI Common Terminology Criteria for Adverse Events) events measured 4 weeks after the last day of reRT.

Secondary Outcome Measures

Name	Time	Method
The key secondary objective is to prospectively validate the palliative efficacy of reRT of DMG. Palliative efficacy is evaluated by two endpoints: overall survival and symptom relief.	4 weeks after end of re-irradiation	Palliative efficacy measured as overall survival will be reported as 1) from date of diagnosis to date of death by any cause, and 2) from date of first radiological and/or clinical progression to date of death by any cause.
Palliative efficacy measured as symptom relief	4 weeks after end of re-irradiation	Symptom relief measured by 1) clinical performance status (Karnofsky or Lansky) assessed every second week, 2) a modified PEDI score before, during and 4 weeks after reRT, 3) steroid dose levels measured every second week, and 4) quality of life monitored before, during and 4 weeks after re-irradiation with PedsQL Cancer module questionnaire.
Other secondary outcomes	through study completion	Other secondary objectives are further defined as: * Image-guided characterization of the anatomical site of progression compared to the primary lesion.; * Assessment of cumulated radiation dose to critical structures in the brain following the initial and reRT treatment.